title: Survey of the effect of genetic variations on gene expression in human prefrontal cortex and its application to genetics of psychiatric disorders.
abstract: Identifying the genetic basis of gene expression variation in the human brain is important for understanding brain physiology and pathophysiology. We investigated the genetic basis of gene expression variation in human prefrontal cortex using single nucleotide polymorphisms (SNPs) and taking into consideration brain sample pH. From approximately 12,000 brain-expressed transcripts, we identified 187 cis-regulated transcripts. Some of the transcripts were identified as cis-regulated in the lymphoblastoid cells or lymphocytes, which suggests common cis-regulation across different tissues. Knowledge of genetic variations contributing to differences in gene expression in the brain would be particularly useful in the study of neuropsychiatric disorders in combination with a large-scale genome-wide association study. Using Wellcome Trust Case Control Consortium association study data, we identified SNPs associated with bipolar disorder and gene expression variation in the human brain. We found that SNPs in the AKAP10 and PRKCI genes are significantly associated with bipolar disorder and gene expression variation.
authors.affiliation: Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. kaziwamoto-tky@umin.ac.jp
authors.forename: Kazuya
authors.initials: K
authors.lastname: Iwamoto
authors.forename: Junko
authors.initials: J
authors.lastname: Ueda
authors.forename: Miki
authors.initials: M
authors.lastname: Bundo
authors.forename: Toshio
authors.initials: T
authors.lastname: Kojima
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Kato
mesh_terms: D000328:Adult; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods; D014644:Genetic Variation / Q000502:physiology*; D005824:Genetics, Behavioral / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019965:Neurocognitive Disorders / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000502:physiology*